Biomimetic sensory feedback through peripheral nerve stimulation improves dexterous use of a bionic hand.

We describe use of a bidirectional neuromyoelectric prosthetic hand that conveys biomimetic sensory feedback. Electromyographic recordings from residual arm muscles were decoded to provide independent and proportional control of a six-DOF prosthetic hand and wrist-the DEKA LUKE arm. Activation of contact sensors on the prosthesis resulted in intraneural microstimulation of residual sensory nerve fibers through chronically implanted Utah Slanted Electrode Arrays, thereby evoking tactile percepts on the phantom hand. With sensory feedback enabled, the participant exhibited greater precision in grip force and was better able to handle fragile objects. With active exploration, the participant was also able to distinguish between small and large objects and between soft and hard ones. When the sensory feedback was biomimetic-designed to mimic natural sensory signals-the participant was able to identify the objects significantly faster than with the use of traditional encoding algorithms that depended on only the present stimulus intensity. Thus, artificial touch can be sculpted by patterning the sensory feedback, and biologically inspired patterns elicit more interpretable and useful percepts.

A nosology of disorders of attention.

The trailblazing research on sleep mechanisms and petit mal epilepsy, conducted during the period from 1940 through 1970, illuminated the brain substrate for normal consciousness and attention, as well as their disorders. This research helped inform and structure our neuropsychologically based model of the "elements" of attention. The model has been used to assess attention in the research laboratory and clinic, and has led to a "nosology of disorders of attention," which is presented here in preliminary form. The nosology reviews the possible causes of the symptom(s) of impaired attention, as well as suggesting a blueprint for future research in this area.

Neonatal auditory activation detected by functional magnetic resonance imaging.

The objective of this study was to detect auditory cortical activation in non-sedated neonates employing functional magnetic resonance imaging (fMRI). Using echo-planar functional brain imaging, subjects were presented with a frequency-modulated pure tone; the BOLD signal response was mapped in 5 mm-thick slices running parallel to the superior temporal gyrus. Twenty healthy neonates (13 term, 7 preterm) at term and 4 adult control subjects. Blood oxygen level-dependent (BOLD) signal in response to auditory stimulus was detected in all 4 adults and in 14 of the 20 neonates. FMRI studies of adult subjects demonstrated increased signal in the superior temporal regions during auditory stimulation. In contrast, signal decreases were detected during auditory stimulation in 9 of 14 newborns with BOLD response. fMRI can be used to detect brain activation with auditory stimulation in human infants.

Regional brain volume abnormalities and long-term cognitive outcome in preterm infants.

CONTEXT: Preterm infants have a high prevalence of long-term cognitive and behavioral disturbances. However, it is not known whether the stresses associated with premature birth disrupt regionally specific brain maturation or whether abnormalities in brain structure contribute to cognitive deficits. OBJECTIVE: To determine whether regional brain volumes differ between term and preterm children and to examine the association of regional brain volumes in prematurely born children with long-term cognitive outcomes. DESIGN AND SETTING: Case-control study conducted in 1998 and 1999 at 2 US university medical schools. PARTICIPANTS: A consecutive sample of 25 eight-year-old preterm children recruited from a longitudinal follow-up study of preterm infants and 39 term control children who were recruited from the community and who were comparable with the preterm children in age, sex, maternal education, and minority status. MAIN OUTCOME MEASURES: Volumes of cortical subdivisions, ventricular system, cerebellum, basal ganglia, corpus callosum, amygdala, and hippocampus, derived from structural magnetic resonance imaging scans and compared between preterm and term children; correlations of regional brain volumes with cognitive measures (at age 8 years) and perinatal variables among preterm children. RESULTS: Regional cortical volumes were significantly smaller in the preterm children, most prominently in sensorimotor regions (difference: left, 14.6%; right, 14.3% [P<.001 for both]) but also in premotor (left, 11.2%; right, 12.6% [P<.001 for both]), midtemporal (left, 7.4% [P =.01]; right, 10.2% [P<.001]), parieto-occipital (left, 7.9% [P =.01]; right, 7.4% [P =.005]), and subgenual (left, 8.9% [P =.03]; right, 11.7% [P =.01]) cortices. Preterm children's brain volumes were significantly larger (by 105. 7%-271.6%) in the occipital and temporal horns of the ventricles (P<. 001 for all) and smaller in the cerebellum (6.7%; P =.02), basal ganglia (11.4%-13.8%; P

Outcome of children in the indomethacin intraventricular hemorrhage prevention trial.

BACKGROUND: For preterm infants, intraventricular hemorrhage (IVH) may be associated with adverse neurodevelopmental outcome. We have demonstrated that early low-dose indomethacin treatment is associated with a decrease in both the incidence and severity of IVH in very low birth weight preterm infants. In addition, we hypothesized that the early administration of low-dose indomethacin would not be associated with an increase in the incidence of neurodevelopmental handicap at 4.5 years of age in our study children. METHODS: To test this hypothesis, we provided neurodevelopmental follow-up for the 384 very low birth weight survivors of the Multicenter Randomized Indomethacin IVH Prevention Trial. Three hundred thirty-seven children (88%) were evaluated at 54 months' corrected age, and underwent neurodevelopmental examinations, including the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R), the Peabody Picture Vocabulary Test-Revised (PPVT-R), and standard neurologic examinations. RESULTS: Of the 337 study children, 170 had been randomized to early low-dose indomethacin therapy and 167 children had received placebo. Twelve (7%) of the 165 indomethacin children and 11 (7%) of the 158 placebo children who underwent neurologic examinations were found to have cerebral palsy. For the 233 English-monolingual children for whom cognitive outcome data follow, the mean gestational age was significantly younger for the children who received indomethacin than for those who received placebo. In addition, although there were no differences in the WPPSI-R or the PPVT-R scores between the 2 groups, analysis of the WPPSI-R full-scale IQ by function range demonstrated significantly less mental retardation among those children randomized to early low-dose indomethacin (for the indomethacin study children, 9% had an IQ <70, 12% had an IQ of 70-80, and 79% had an IQ >80, compared with the placebo group, for whom 17% had an IQ <70, 18% had an IQ of 70-80, and 65% had an IQ >80). Indomethacin children also experienced significantly less difficulty with vocabulary skills as assessed by the PPVT-R when compared with placebo children. CONCLUSIONS: These data suggest that, for preterm neonates, the early administration of low-dose indomethacin therapy is not associated with adverse neurodevelopmental function at 54 months' corrected age.

Spontaneously infected cephalohematoma: case report and review of the literature.

Spontaneously infected cephalohematomas are rare occurrences; only five cases have been reported previously. Uninfected cephalohematomas are common and usually resolve without treatment. However, physicians should be aware that cephalohematomas are potential sites for infection and may require aspiration for diagnosis and treatment. Untreated infected cephalohematomas may lead to osteomyelitis, epidural abscess, or subdural empyema. We present a case of a spontaneously infected cephalohematoma with an associated osteomyelitis which was successfully managed with drainage and long-term antibiotics. A review of the literature is also presented.

Relationship between prior course of illness and neuropsychological functioning in patients with bipolar disorder.

BACKGROUND: This study investigated the relationship between prior course of illness and neuropsychological deficits in relatively high functioning outpatients with bipolar disorder. METHOD: Forty-nine bipolar I or II patients, in a relatively euthymic state during treatment with mood stabilizers, were administered neuropsychological tests that assessed a variety of functions, including verbal memory, sustained attention and vigilance, and intelligence. A detailed retrospective life chart was completed for each patient using the NIMH Life Chart Method" to define variables reflecting duration and severity of illness, and frequency of episodes. RESULTS: Stepwise multiple regression analyses show that several different measures of a more severe course of prior illness related to greater duration and a larger number of affective episodes and hospitalizations were associated with poorer performance on tests of abstraction, attention and memory. CONCLUSION: The results indicate that bipolar patients with a more severe prior course of illness and a greater number of affective episodes have more impaired neuropsychological functioning. The direction of causality and the pathophysiological mechanisms remain to be explored.

Sex differences in seasonal variations in P300.

Previous reports of seasonal variations in P300 were based on cross-sectional observations of subjects tested at different times of the year. In this study, we tested three groups of subjects in each of two seasons: winter and spring, spring and summer, and summer and winter. We found winter or spring maxima in auditory and visual P300 and visual slow wave. This pattern of results, with the amplitude of P300 being inversely related to the amount of sunlight in a season, supports the hypothesis that the allocation of processing resources varies across the seasons. Our results also suggest a trend for an increased sensitivity of women, as compared with men, to seasonal influences on P300. Although our findings do not provide strong evidence that P300 varies systematically as a function of season, seasonal factors appear to affect cognitive processing (as indexed by P300) differentially in men and women.

Minimal head trauma in children revisited: is routine hospitalization required?

OBJECTIVE: Children with a question of occult head injury are routinely hospitalized despite having both normal central nervous system (CNS) and computed tomographic (CT) scan examinations. We determined the incidence of significant CNS morbidity after occult head injury to determine whether or not hospital admission was necessary in children after minimal head trauma. METHODS: We reviewed the records of children admitted to a level I trauma center with a question of closed head injury, an initial Glasgow Coma Scale equal to 15, a normal neurologic exam, and a normal head CT scan. Children with associated injuries requiring admission were excluded. The endpoints were deterioration in CNS exam, new CT findings, and the need for a prolonged hospital stay. RESULTS: Sixty-two patients were studied with a mean age of 7 years (range, 1 month to 15 years), and 65% were male. The primary mechanisms of injury were fall (45%) and vehicular crash (23%). The mean injury severity score was 4 +/- 2. The mean length of stay was 1.2 days (range, 1 to 3 days). Prolonged hospitalization occurred in 9 patients (15%). No child developed significant CNS sequelae warranting hospital admission. Total charges for these hospitalizations were $177 874. CONCLUSIONS: Children undergoing emergency department work-up of occult head injury, who have a normal CNS exam and a normal head CT scan, do not seem to be at risk for significant CNS sequelae. These patients can be discharged home with parental supervision and avoid unnecessary and costly hospitalization.

Three cases of symptom change in Tourette's syndrome and obsessive-compulsive disorder associated with paediatric cerebral malignancies.

OBJECTIVE: To correlate behaviour manifestations with tumour location in three children who had Gilles de la Tourette's syndrome (GTS), obsessive-compulsive disorder (OCD), and primary cerebral malignancies. METHOD: Cases were ascertained from a chart review in a GTS and OCD specialty clinic. For each case the temporal progression of change in neuropsychiatric symptoms was qualitatively correlated with radiographic documentation of tumour progression. RESULTS: The change in symptom severities during tumour progression and treatment, together with prior neurobiological studies of GTS, suggest that the ventral striatum, corpus callosum, thalamus, and midbrain are potentially important neural substrates in the formation or modulation of tic symptoms. The limbic system, including the hypothalamus and cingulate, and the caudate nucleus, seem to be important in the neurobiology of OCD. All structures are neuroanatomically and functionally related to the corticostriato-thalamocortical circuitry that is thought to subserve symptom generation in both GTS and OCD. CONCLUSION: Although the malignancies were not likely to have caused the tic and OCD symptoms in these children, the locations of these intracranial lesions provide important clues in identifying brain regions that may contribute to the determination of tic and OCD severities.

Neurodevelopmental outcome at 36 months' corrected age of preterm infants in the Multicenter Indomethacin Intraventricular Hemorrhage Prevention Trial.

OBJECTIVES: Low-dose indomethacin has been shown to prevent intraventricular hemorrhage (IVH) in very low birth weight neonates, and long-term neurodevelopmental follow-up data are needed to validate this intervention. We hypothesized that the early administration of low-dose indomethacin would not be associated with adverse cognitive outcome at 36 months' corrected age (CA). METHODS: We enrolled 431 neonates of 600 to 1250 g birth weight with no IVH at 6 to 12 hours in a randomized, prospective trial to determine whether low-dose indomethacin would prevent IVH. A priori, neurodevelopmental follow-up examinations, including the Stanford-Binet Intelligence Scale and Peabody Picture Vocabulary Test-Revised, and standard neurologic examinations were planned at 36 months' CA. RESULTS: Three hundred eighty-four of the 431 infants survived (192 [92%] of 209 infants receiving indomethacin versus 192 [86%] of 222 infants receiving saline), and 343 (89%) children were examined at 36 months' CA. Thirteen (8%) of the 166 infants who received indomethacin and 14 (8%) of 167 infants receiving the placebo were found to have cerebral palsy. There were no differences in the incidence of deafness or blindness between the two groups. For the 248 English-monolingual children for whom IQ data follow, the mean gestational age was significantly younger for the infants who received indomethacin than for those who received the placebo. None of the 115 infants who received indomethacin was found to have ventriculomegaly on cranial ultrasound at term, compared with 5 of 110 infants who received the placebo. The mean +/- SD Stanford-Binet IQ score for the 126 English-monolingual children who had received indomethacin was 89.6 +/- 18.92, compared with 85.0 +/- 20.79 for the 122 English-monolingual children who had received the placebo. Although maternal education was strongly correlated with Stanford-Binet IQ at 36 months' CA, there was no difference in educational levels between mothers of the infants receiving indomethacin and the placebo. CONCLUSIONS: Indomethacin administered at 6 to 12 hours as prophylaxis against IVH in very low birth weight infants does not result in adverse cognitive or motor outcomes at 36 months' CA.

Circadian profiles of cortisol, prolactin, and thyrotropin in seasonal affective disorder.

To determine whether circadian profiles of various plasma hormones are abnormal in patients with winter seasonal affective disorder (SAD), we obtained 24-hour profiles of plasma cortisol, prolactin, and thyrotropin in subsets of a sample of 22 depressed patients with SAD on and off light therapy and in subsets of a sample of 24 normal controls. Cortisol levels did not differ between patients and controls, and levels in patients were not affected by light therapy. Prolactin levels were lower in patients than in controls throughout the day (p < 0.03) but were unaffected by light therapy. Independent of patient vs. control status, prolactin levels were higher in women than in men throughout the day (p < 0.003). Thyrotropin levels were no different in patients and controls, but levels in patients were lower following light therapy (p < 0.05).

Diagnosis-related group refinement with diagnosis- and procedure-specific comorbidities and complications.

Diagnosis-related groups have been revised through more refined uses of secondary diagnoses. Under the refined diagnosis-related groups, patients are distinguished with respect to classes of secondary diagnoses that are disease- and procedure-specific. Each class represents a different level of utilization for a given principal diagnosis or surgical procedure. The refined system was evaluated with national data from the Medicare program. Estimates of hospital costs and utilization based on refined diagnosis-related groups were more precise than those based on unrefined diagnosis-related groups. This approach to diagnosis-related group refinement does not represent a radical departure from the current diagnosis-related group framework and does not require new data collection efforts. Moreover, a payment system based on the refined model is less affected by the ordering of the diagnoses than under the existing diagnosis-related group system. How the refined diagnosis-related group framework can accommodate future refinements at all levels of the classification scheme is also discussed.

Antenatal steroids, delivery mode, and intraventricular hemorrhage in preterm infants.

OBJECTIVE: The relationship between antenatal steroids, delivery mode, and early-onset intraventricular hemorrhage was examined in very-low-birth-weight infants. STUDY DESIGN: A total of 505 preterm infants (birth weight 600 to 1250 gm) were enrolled in a multicenter, prospectively randomized, controlled trial evaluating the efficacy of postnatal indomethacin to prevent intraventricular hemorrhage. All infants had echoencephalography between 5 and 11 hours of life. RESULTS: Seventy-three infants had intraventricular hemorrhage within the first 5 to 11 hours (mean age at echoencephalography 7.5 hours). Four hundred thirty-two infants did not have early intraventricular hemorrhage. There was less antenatal steroid treatment (19% vs 32%, p = 0.03) and more vaginal deliveries (71% vs 45%, p < 0.0001) in the group with early intraventricular hemorrhage. Of 152 infants who received antenatal steroids, those delivered by cesarean section had significantly less early-onset intraventricular hemorrhage than did those delivered vaginally (4% vs 17%, p = 0.02). Of the 353 not exposed to antenatal steroids, 10% of infants delivered by cesarean section and 22% delivered vaginally had early intraventricular hemorrhage (p = 0.003). CONCLUSION: These data are the first to suggest that both antenatal steroids and cesarean section delivery have an important and independent role in lowering the risk of early-onset intraventricular hemorrhage.

Neuroendoscopic laser-assisted ventriculostomy of the third ventricle.

Hydrocephalus is caused by an imbalance between the production and absorption of cerebrospinal fluid. Ventriculostomy of the third ventricle now is an acceptable treatment alternative for this problem. This procedure reduces costs over the course of the illness because the patient does not require subsequent shunt revisions throughout his or her life. The specialized care and the fear associated with the dependency on mechanical hardware also are eliminated if shunt placement is avoided. Postoperative complications may include increased intracranial pressure, bleeding, infection, and pain.

Costs of potential complications of care for major surgery patients.

We examined computerized hospital discharge abstract data from 372,680 major surgery patients admitted to 404 California acute care hospitals in 1988 to identify potential complications of care. At least one potential in-hospital complication occurred for 10.8% of patients. Patients with complications were older and more likely to die in-hospital (9.4% compared to 1.0%, P < 0.0001). On average, patients with complications had longer stays (13.5 versus 5.4 days, p < 0.0001) and higher total charges ($30,896 versus $9,239, p < 0.0001). After adjusting for demographic, clinical, and hospital factors, patients with potential complications averaged $16,023 higher total hospital charges than uncomplicated patients. Complications were associated with 96.6% (95% confidence interval = 95.2%, 98.0%) higher hospital charges after adjusting for these factors. Across all patients, complications were related to over $647 million in additional total hospital charges for these major surgery patients.

Season, gender, and P300.

Light therapy in patients with seasonal affective disorder has been reported to enhance visual P300 amplitude. This findings raises the possibility that variations in P300 occur naturally in nonpatients as a function of seasonal variation in sunlight. In the present investigation, P300 was studied in a sample of psychiatrically screened normal subjects who were tested at different times of the year. P300 was larger in women than men and varied in relation to season. This pattern is relevant to studies in which subjects are tested under varying sunlight conditions, such as different seasons. In addition, variations in P300 in normal subjects may be relevant to an understanding of the effectiveness of light therapy for patients with seasonal affective disorder.

Developmental dyslexia and attention dysfunction in adults: brain potential indices of information processing.

Event-related brain potentials (ERPs) were recorded from a group of 13 men with severe developmental dyslexia and 15 matched normal controls. Auditory and visual stimuli, presented in separate reaction time tasks of graded difficulty, were used to elicit ERPs. No group differences in P300 were seen under relatively undemanding task conditions. However, as task demands increased, visual P300 was reduced in the dyslexic men as compared with the normal readers. An Abbreviated Conners Parent Rating Scale was used to assess retrospectively childhood symptoms of attention-deficit hyperactivity disorder (ADHD). Additional analyses revealed that the dyslexics with a history of many symptoms of ADHD in childhood (high ADHD) accounted for the group differences in P300; the dyslexics with a history of few or no such symptoms (low ADHD) were indistinguishable from the controls at all electrode sites. Furthermore, whereas the low-ADHD dyslexics showed the same hemispheric asymmetry in auditory P300 as did the controls (right > left), auditory P300 was more symmetrically distributed in the high-ADHD dyslexics. The results are interpreted as suggesting that a distinct brain organization may characterize dyslexic men with a history of concomitant deficits in attention.

Sleep in fall/winter seasonal affective disorder: effects of light and changing seasons.

Disturbances of sleep are a hallmark of seasonal affective disorders (SAD), as they are of other mood disorders. Fall/winter SAD patients most often report hypersomnia. Among responses of 293 SAD patients on a symptom questionnaire, complaints of winter hypersomnia (80%) greatly exceeded insomnia (10%), hypersomnia plus insomnia (5%), or no sleep difficulty (5%). Increased sleep length in fall/winter is not unique to SAD. Among 1571 individuals across four latitudes surveyed at random from the general population, winter sleep increases of < or = 2 hr/day relative to summer were reported by nearly half. However, hypersomnia had a low correlation (r = 0.29) with the total number of other SAD symptoms that were reported in this sample. Ten SAD patients kept daily sleep logs across 1 yr that showed increases in fall and winter (sleeping most in October; least in May) whose maximum averaged 2.7 hr per day more weekend sleep than in spring and summer. These winter increases might have been somewhat attenuated since most received light therapy during part of the winter. Nocturnal EEG recordings of depressed SAD patients in winter showed decreased sleep efficiency, decreased delta sleep percentage, and increased REM density (but normal REM latency) in comparison with recordings: (1) from themselves in summer; (2) from themselves after > or = 9 days of light therapy; or (3) from age- and gender-matched healthy controls. Thus, the extent of fall/winter oversleeping recorded by our SAD patients did not differ dramatically from that reported by the general population, but sleep complaints of our SAD patients have been accompanied by features of sleep architecture that are different from healthy controls and are reversed by summer or by bright-light therapy.

Low-dose indomethacin and prevention of intraventricular hemorrhage: a multicenter randomized trial.

OBJECTIVES: Parenchymal involvement of intraventricular hemorrhage (IVH) is a major risk factor for neurodevelopmental handicap in very low birth weight neonates. Previous trials have suggested that indomethacin would lower the incidence and severity of IVH in very low birth weight neonates. METHODS: We enrolled 431 neonates of 600- to 1250-g birth weight with no evidence for IVH at 6 to 11 hours of age in a prospective, randomized, placebo-controlled trial to test the hypothesis that low-dose indomethacin (0.1 mg/kg intravenously at 6 to 12 postnatal hours and every 24 hours for two more doses) would lower the incidence and severity of IVH. Serial cranial ultrasound examinations and echocardiographs were performed. RESULTS: There were no differences in the birth weight, gestational age, sex, Apgar scores, and percent of neonates treated with surfactant between the indomethacin and placebo groups. Within the first 5 days, 25 (12%) indomethacin-treated and 40 (18%) placebo-treated neonates developed IVH (P = .03, trend test). Only one indomethacin-treated patient experienced grade 4 IVH compared with 10 placebo-treated neonates (P = .01). Sixteen indomethacin-treated neonates and 29 control neonates died (P = .08); there was a difference favoring indomethacin with respect to survival time (P = .06). Eighty-six percent of all neonates had a patent ductus arteriosus on the first postnatal day; indomethacin was associated with significant ductal closure by the fifth day of life (P < .001). There were no differences in adverse events attributed to indomethacin between the two treatment groups. CONCLUSIONS: Low-dose prophylactic indomethacin significantly lowers the incidence and severity of IVH, particularly the severe form (grade 4 IVH). In addition, indomethacin closes the patent ductus arteriosus and is not associated with significant adverse drug events in very low birth weight neonates.